MicroRNA-195 rescues the impaired MS-dCA1 neural circuit and spatial memory in rats with chronic cerebral hypoperfusion

¹ Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China

Advanced Neurology 2022, 1(2), 116 https://doi.org/10.36922/an.v1i2.116

Submitted: 30 May 2022 | Accepted: 9 August 2022 | Published: 30 August 2022

© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Chronic cerebral hypoperfusion (CCH) is a common risk factor for vascular dementia and Alzheimer’s disease (AD). The previous studies have shown that CCH-induced multiple AD-like pathological changes in the hippocampus and cortex through downregulating the microRNA-195 (miR-195) expression. However, whether and how miR-195 participates in the dysfunction of the medial septum (MS)-dorsal hippocampal CA1 (dCA1) neural circuit following CCH is still obscure. In the present study, we found that miR-195 was downregulated in the MS region of CCH rats. Moreover, using electrophysiological recording and immunofluorescence staining technique, we found that the knockdown of miR-195 through the injection of lenti- AMO-195 into the MS region led to a pathological change that mimicked the damage to the MS-dCA1 neural circuit in CCH rats, including the decreased input-output (I/O) curve, increased paired-pulse ratio (PPR), decreased numbers of ChAT⁺ and PV⁺ neurons in MS, and diminished theta rhythm in the hippocampus. More importantly, exogenously supplemented miR-195 into the MS region rescued the damaged neural circuit in MS-dCA1 of CCH rats by injecting lenti-pre-miR-195. Gain-of-function of miR-195 in the MS region significantly improved the cognitive dysfunction in CCH rats assessed by the Morris water maze test. In conclusion, knockdown of miR-195 in the MS region can impair MS-dCA1 neural circuit function, while upregulation of miR- 195 can rescue the impaired function of MS-dCA1 neural circuit and spatial memory ability in CCH rats. This provides a valuable reference for future anti-dementia therapy involving miR-195.

Keywords

Chronic cerebral hypoperfusion

MicroRNA-195

Medial septum-dorsal hippocampal CA1 neural circuit

Funding

National Science and Technology Innovation 2030 - Major program of “Brain Science and Brain-Like Research”

National Natural Science Foundation of China

Key Research and Development Program of Heilongjiang Province

Heilongjiang Touyan Innovation Team Program

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Conflict of interest

The authors declare that they have no conflicts of interest to report.

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